Specific effect of arachidonic acid on 17beta-hydroxysteroid dehydrogenase in rat Leydig cells.
It is well known that arachidonic acid (AA) acts as an intratesticular factor regulating luteinizing hormone-mediated testicular steroidogenesis. The present studies were conducted to determine the effect of AA on steroidogenic enzymes in rat Leydig cells. Exogenously added AA significantly inhibited 22(R)-hydroxy-cholesterol-stimulated testosterone production, which is a clear indication that AA is acting at some point after cholesterol transport to the inner mitochondrial membrane. AA failed to block the conversion of 22(R)-hydroxycholesterol to pregnenolone, indicating that the cytochrome P-450 side-chain cleavage enzyme complex is not the site of inhibition. The present results demonstrate that only 17beta-hydroxysteroid dehydrogenase seems to be involved in the AA action, since nearly 60% inhibition of testosterone production was found when the cells were incubated with androstenedione. Furthermore, no effect of AA was found when androstenediol was used as substrate in the testosterone synthesis, which indicates that 3beta-hydroxysteroid dehydrogenase is not affected by AA. The conversion of AA to its metabolites is not required for its action on 17beta-hydroxysteroid dehydrogenase and the activation of protein kinase C is not involved in the inhibitory effect.
Marinero
M J
MJ
Unidad de Neuroendocrinologia Molecular, Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares-Madrid, Spain.
Penalva
V
V
Oliva
J L
JL
Colás
B
B
Prieto
J C
JC
López-Ruiz
M P
MP
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015114:Androstenediol / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D006888:Hydroxycholesterols / Q000378:metabolism; D007985:Leydig Cells / Q000201:enzymology*; D008297:Male; D011284:Pregnenolone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000096:biosynthesis / Q000378:metabolism
D006888:Hydroxycholesterols; C003585:22-hydroxycholesterol; D016718:Arachidonic Acid; D013739:Testosterone; D000735:Androstenedione; D011284:Pregnenolone; D015114:Androstenediol; D002784:Cholesterol; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases